Video Experimental Relacionado

Updated: Sep 10, 2025

Identification of Pharmaceuticals in The Aquatic Environment Using HPLC-ESI-Q-TOF-MS and Elimination of Erythromycin Through Photo-Induced Degradation

Identification of Pharmaceuticals in The Aquatic Environment Using HPLC-ESI-Q-TOF-MS and Elimination of Erythromycin Through Photo-Induced Degradation

Published on: August 1, 2018

Una perspectiva catalítica sobre la hidrólisis de la eritromicina por la eritromicina esterasa C: estudio combinado

Abhishek Bera¹, Niladri Patra¹

¹Department of Chemistry & Chemical Biology, Indian Institute of Technology (ISM) Dhanbad, Dhanbad-826004, India.

Journal of chemical information and modeling

|August 22, 2025

Resumen

Las esterasas macrolides como EreC inactivan los antibióticos. Este estudio revela los cambios conformacionales dependientes del pH de EreC y el mecanismo detallado de la hidrólisis de la eritromicina utilizando métodos QM/MM.

Área de la Ciencia:

La bioquímica
Biología molecular
Química computacional

Sus antecedentes:

Las esterasas macrolides son enzimas clave en la resistencia bacteriana a los antibióticos.
Estas enzimas hidrolizan los antibióticos macrólidos, reduciendo su eficacia.
La eritromicina esterasa C (EreC) es una enzima inactivadora significativa de los macrolidos.

Objetivo del estudio:

Investigar el mecanismo catalítico de la hidrólisis de la eritromicina mediante EreC.
Para explorar la influencia del pH en la conformación y actividad de EreC.
Aclarar el papel de los residuos específicos del sitio activo en el proceso de hidrólisis.

Principales métodos:

Simulaciones de mecánica cuántica y mecánica molecular.
Simulaciones de dinámica molecular de pH constante (CpHMD).
Simulaciones de metadinámica QM/MM.

Principales resultados:

Identificación del cambio conformacional dependiente del pH del EreC, modulado por Glu78 y Glu300.
Reveló un pKa reducido de His50 debido a cambios en el microambiente, lo que permite su papel como base general.
Delineó el mecanismo de hidrólisis en dos pasos e identificó los residuos clave (Glu78, Arg261, His289) cruciales para la catálisis.

Conclusiones:

La actividad de EreC es sensible al pH, lo que implica cambios conformacionales.
La díada catalítica Glu47-His50 juega un papel crucial en la hidrólisis de la eritromicina.
Este estudio proporciona una comprensión mecánica detallada de esta hidrolasa independiente de los metales.

Más Videos Relacionados

The Logic, Experimental Steps, and Potential of Heterologous Natural Product Biosynthesis Featuring the Complex Antibiotic Erythromycin A Produced Through E. coli

The Logic, Experimental Steps, and Potential of Heterologous Natural Product Biosynthesis Featuring the Complex Antibiotic Erythromycin A Produced Through E. coli

Published on: January 13, 2013

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

Published on: July 19, 2019

Videos de Conceptos Relacionados

Nonlinear Pharmacokinetics: Michaelis-Menten Equation

Nonlinear Pharmacokinetics: Michaelis-Menten Equation

The Michaelis–Menten equation is a fundamental model for describing capacity-limited kinetics in drug metabolism. It offers insights into the rate of decline of plasma drug concentration Cp over time, with Vmax and KM as pivotal parameters.
Vmax represents the maximum achievable process rate, while KM, known as the Michaelis constant, signifies the drug concentration at which the process rate reaches half its maximum. This relationship between Vmax, KM, and Cp gives rise to three distinct...

Determination of Michaelis Constant and Maximum Elimination Rate

Determination of Michaelis Constant and Maximum Elimination Rate

The Michaelis constant (KM) and the theoretical maximum process rate (Vmax) are vital parameters in the Michaelis-Menten equation, central to many biochemical reactions. They provide essential insights into enzyme kinetics and drug metabolism.
These parameters can be estimated by analyzing plasma concentration data post-drug administration. A notable example of this application is phenytoin, a drug with capacity-limited kinetics. It's recommended that phenytoin should be administered at two...

Catalytically Perfect Enzymes

Catalytically Perfect Enzymes

The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.

Most enzymes...

E2 Reaction: Kinetics and Mechanism

E2 Reaction: Kinetics and Mechanism

SN2 substitutions and E2 eliminations of alkyl halides proceed via a concerted pathway. While the nucleophile attacks the alpha carbon in SN2 reactions, it functions as a strong base and abstracts a beta hydrogen in the E2 mechanism. The rate-limiting transition state in E2 elimination reactions is characterized by partially broken carbon–hydrogen and carbon–halogen bonds and a partially formed pi bond between the alpha and beta carbons. The beta hydrogen and halide are eliminated...

E1 Reaction: Kinetics and Mechanism

E1 Reaction: Kinetics and Mechanism

Here, in contrast to the E2 reaction mechanism, we delve into the aspects of the E1 reaction mechanism, which has two steps: rate-limiting loss of the leaving group and abstraction of the beta hydrogen by a weak base. Typically, the experimental proof for the E1 mechanism is via kinetic studies or isotope studies. While the former demonstrates the first-order kinetics—the dependence of the reaction solely on substrate concentration—the latter proves the abstraction of hydrogen only...